We have begun this project by targeting 5 candidate genes identified by the Undiagnosed Diseases Program. Initially we used TALEN technology to target alleles. WE are collaborating with Dr. Raman Sood and the NHGRI zebrafish core to inject and screen these TALEN's for mutagenic activity. We have identified successful activity for SMS, GEMIN5, SUSD4, and WARS2. We will raise these fish, outcross, identify carriers, and inbreed carrier siblings. Each gene will be phenotyped and any observable phenotypes will be compared to the human pathology. Going forward, we are switching mutagenesis technology from TALEN's to the newly described CRISPR/Cas technology. We will be able to increase throughput approximately 5 fold with this technology, allowing us to ultimately mutagenize all the candidate genes generated in the UDP initiative.